1. Field of the Invention
The present invention relates to novel and pharmaceutically useful thienotriazolodiazepine compounds and pharmaceutically acceptable acid addition salts thereof, and pharmaceutical uses thereof.
2. Description of the Prior Art
Certain s-triazolo[3,4-c]thieno[2,3-e][1,4]diazepine compounds represented by 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo[3,4-c]thieno[2,3-e][1,4] diazepine [hereinunder referred to as Etizolam (Recommended INN)] are known to exhibit useful pharmacological activities against the central nervous system such as antianxiety or anticonvulsant activities as disclosed in U.S. Pat. No. 3,904,641.
Japan. J. Pharmacol., vol. 44, p. 381-391 (1987) discloses that Etizolam exhibits antagonistic activity on platelet-activating factor (hereinunder referred to as PAF), and further EP-A 194416 discloses that s-triazolo[3,4-c]thieno[2,3-e][1,4]diazepine-carboxylic acid amide compounds also exhibit antagonistic activity on PAF.
Benveniste et al. found a factor which strongly induced platelet aggregation from rabbit basophils, and named as platelet-activating factor (PAF) in 1972. Hanahan et al. identified that the factor was phosphoglyceride of alkyl ether type having acetyl group in the 2-position, i.e. 1-O-hexadecyl or octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, in 1980.
The physiological roles of PAF have been intensively investigated, and it has been known that PAF was an important factor of various physiological reactions inclusive of platelet aggregation, reduction in blood pressure, immediate allergic reaction, contraction of smooth muscle, inflammation, pain, edema, as well as alteration in the respiratory and circulatory systems.
Therefore, PAF-antagonistic activity-possessing compounds are considered to be very useful for various PAF-induced diseases such as inflammatory diseases, allergic diseases, anaphylactic shocks, septic shocks, vascular diseases as DIC, myocardial diseases, asthma, pulmonary edema, adult respiratory diseases.
Recently, certain s-triazolo[3,4-c]thieno[2,3-e][1,4]diazepine compounds have been shown to exhibit PAF-antagonistic activity as described above. However such compounds are not sufficient in view of the separation from the effect on the central nervous system, the potency, the effectiveness by the oral administration or the duration of activity. Therefore, it is desirable to provide potent PAF-antagonistic thienotriazolodiazepine compounds which possess not only effectiveness by oral administration and long-lasting effect, but also less inhibitory effect on the central nervous system.